Phosphoserine phosphatase is expressed in the neural stem cell niche and regulates neural stem and progenitor cell proliferation.

Department of Neurological Surgery, UCLA, Los Angeles, CA 90095-1769, USA.
Stem Cells (Impact Factor: 6.52). 09/2007; 25(8):1975-84.
Source: PubMed


Phosphoserine phosphatase (PSP) metabolizes the conversion of l-phosphoserine to l-serine, classically known as an amino acid necessary for protein and nucleotide synthesis and more recently suggested to be involved in cell-to-cell signaling. Previously, we identified PSP as being enriched in proliferating neural progenitors and highly expressed by embryonic and hematopoietic stem cells, suggesting a general role in stem cells. Here we demonstrate that PSP is highly expressed in periventricular neural progenitors in the embryonic brain. In the adult brain, PSP expression was observed in slowly dividing or quiescent glial fibrillary acidic protein (GFAP)-positive cells and CD24-positive ependymal cells in the forebrain germinal zone adjacent to the lateral ventricle and within GFAP-positive cells of the hippocampal subgranular zone, consistent with expression in adult neural stem cells. In vitro, PSP overexpression promoted proliferation, whereas small interfering RNA-induced knockdown inhibited proliferation of neural stem cells derived from embryonic cortex and adult striatal subventricular zone. The effects of PSP knockdown were partially rescued by exogenous l-serine. These data support a role for PSP in neural stem cell proliferation and suggest that in the adult periventricular germinal zones, PSP may regulate signaling between neural stem cells and other cells within the stem cell niche. Disclosure of potential conflicts of interest is found at the end of this article.

Download full-text


Available from: Joseph Dougherty, Nov 05, 2014
  • Source
    • "During this period, type C and A cells, which incorporated BrdU, start to differentiate and migrate out of the SVZ. Therefore, after the wash-out period, only slowly-dividing cells, which include type B cells, can be detected in the SVZ (Doetsch et al., 1999; Morshead et al., 1994; Nakano et al., 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Neural stem cells (NSCs) in the adult brain have been a consistent focus of biomedical research largely because of their potential clinical application. To fully exploit this potential, the molecular mechanisms that regulate NSCs must be clarified. Several lines of evidence show that a multifunctional protein, Galectin-1, is expressed and has a functional role in a subset of adult NSCs. Researchers, including our group, have explored the physiological role of Galectin-1 in NSCs and its application in the treatment of animal models of neurological disorders such as brain ischemia and spinal cord injury. Here, we summarize what is currently known regarding the role of Galectin-1 in adult NSCs. Furthermore, we discuss current issues in researching the role of Galectin-1 in adult NSCs under both physiological and pathological conditions.
    Full-text · Article · Jul 2012 · Developmental Neurobiology
  • Source
    • "Provocatively, PSP is specifically expressed by GFAP-expressing progenitors within the subventricular zone (a region of ongoing adult neurogenesis (Doetsch, 2003)) and is present in only a subset of 3-PGDH-expressing cells within this area (Nakano et al., 2007). This suggests that while many cells within the neurogenic regions may synthesize P-Ser, only some of these cells are capable of further metabolizing it to L-serine and removing P-Ser from their local microenvironment. "
    [Show abstract] [Hide abstract]
    ABSTRACT: High-throughput identification of small molecules that selectively modulate molecular, cellular, or systems-level properties of the mammalian brain is a significant challenge. Here we report the chemical genetic identification of the orphan ligand phosphoserine (P-Ser) as an enhancer of neurogenesis. P-Ser inhibits neural stem cell/progenitor proliferation and self-renewal, enhances neurogenic fate commitment, and improves neuronal survival. We further demonstrate that the effects of P-Ser are mediated by the group III metabotropic glutamate receptor 4 (mGluR4). siRNA-mediated knockdown of mGluR4 abolished the effects of P-Ser and increased neurosphere proliferation, at least in part through upregulation of mTOR pathway activity. We also found that P-Ser increases neurogenesis in human embryonic stem cell-derived neural progenitors. This work highlights the tremendous potential of developing effective small-molecule drugs for use in regenerative medicine or transplantation therapy.
    Full-text · Article · Oct 2007 · Chemistry & Biology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A design for a simulation of autonomous agents acting in a physical environment is outlined. The simulation is concurrent object-oriented in design using a continuum of message passing protocols. Messages, which account for interaction between all simulation objects, are non-symbolic and tightly coupled to the methods used for their interpretation. This coupling is expressed through the use of meta-methods which constrain the relationship of classes of messages with respect to classes of methods. Modeling is endomorphic and support is provided for the construction of dynamic modeling hierarchies internal to the agent. The dispersal of messages through such a hierarchy is discussed with respect to issues of aggregation and subsumption with special attention being given to realization of reflective computation in such an architecture
    Full-text · Conference Paper · May 1991
Show more